Acute pancreatitis (AP) is a common abdominal inflammatory disease. Disturbed gut homeostasis secondary to pancreatic inflammation aggravates the condition retroactively. Probiotic Clostridium butyricum (C. butyricum) strains with immunomodulatory effects are known to suppress intestinal inflammation. The current study investigated potential beneficial effects of C. butyricum strains on AP and underlying mechanisms.
Experimental AP or severe AP (SAP) was induced by caerulein hyperstimulation or caerulein hyperstimulation together with lipopolysaccharide. Two C. butyricum strains MIYAIRI 588 (CBM588) and CGMCC0313.1 (CB0313.1) were supplemented to mice for three weeks before AP or SAP induction. We found that both CBM588 and CB0313.1 protected against experimental AP, as evidenced by reduced serum amylase and lipase levels, pancreatic edema and myeloperoxidase activity. Amelioration of both experimental AP and SAP by CB0313.1 indicated a non-model specific effect. Moreover, C. butyricum inhibited pancreatic neutrophil and dendritic cell infiltration, NLRP3 inflammasome activation as well as pro-inflammatory signaling pathways. Additionally in the gut, C. butyricum strains attenuated AP-associated intestinal inflammation and barrier dysfunction. Reduced penetration of pathogenic bacteria Escherichia coli and Enterococcus in pancreas was observed as a result of reinforced gut barrier function. Gut microbiome analyses further revealed that beneficial effects of C. butyricum on pancreatic-gut homeostasis were correlated with improved gut dysbiosis. In particular, relative abundance of Desulfovibrionaceae decreased, and Verrucomicrobiaceae Clostridiaceae and Lactobacillaceae increased.
We for the first time demonstrate a protective effect of C. butyricum in AP by modulating intestinal homeostasis. This study identifies feasible probiotic-candidates for AP treatment in clinical settings. This article is protected by copyright. All rights reserved.